Periodic Reporting for period 1 - FLAVIVACCINE (Development and characterization of a pan-flavivirus vaccine candidate)
Reporting period: 2024-01-01 to 2025-06-30
Viruses causing dengue, Zika, yellow fever and West Nile fever are transmitted by mosquitoes. Annually, they cumulatively infect half a billion people, cause 250,000 deaths, and threaten nearly the entire human population, representing a tremendous global health burden. More alarmingly, in a context of human-driven global changes, these viral threats will intensify with larger and more frequent epidemics, potentially leading to pandemics in the EU, will expand with geographic spreading of the mosquito vectors and encroaching the entire EU, and will multiply with the likely emergence of yet-unknown mosquito-borne viruses. Improving pandemic preparedness and response to these emerging and re-emerging diseases is a top priority both for the EU and WHO. However, there are no effective interventions against all these mosquito-borne viruses and current vaccines targeting viral proteins have severe safety issues. FLAVIVACCINE’s ambition is to develop a novel, broad-spectrum, mosquito saliva-targeted vaccine candidate that protects against multiple different flaviviruses and is ready for clinical evaluation. FLAVIVACCINE will define the immunogenicity of the pan-flavivirus target, develop and characterize a vaccine candidate against multiple flaviviruses, and prepare it for clinical evaluation. To reach these goals, FLAVIVACCINE creates a unique interdisciplinary environment of ten public and private institutions, including Universities, Research Institutions and a Vaccine Developer, from seven countries to cover all the required scientific expertise and knowledge in cell biology, virology, immunology and vaccinology. The pan-flavivirus vaccine candidate that will be validated against dengue, yellow fever, Zika and West Nile diseases in several preclinical models, together with the knowledge and networks resulting from FLAVIVACCINE, will have short- and long-term impact on the EU ability to combat epidemic and pandemic viral threats, and protect communities and citizens in the EU and around the world.
FLAVIVACCINE consortium made substantial progress toward defining the immunogenicity of the selected mosquito-derived vaccine target. Partners developed robust methodologies to isolate and characterize these components from different mosquito cell lines, describing proteomic and biophysical profiles. Immunization studies in mice demonstrated the induction of specific antibody responses, with variability depending of the injection route, and provided the first evidence of target-specific IgG. Complementary assays for T cell activation were optimized, enabling more precise assessment of cellular responses. In parallel, several candidate antigens were produced and evaluated in vivo: while they elicited antibody responses, they did not confer protection, highlighting the need for refined antigen discovery. Using proteomic approaches, co-immunoprecipitation, and immuno-reactive profiling, the consortium identified a second panel of antigenic proteins, four of which are now undergoing further in vivo testing. The addition of a new partner through the WIDERA scheme will increase our antigen identification capacity. We delimited the conditions for vaccine protection in different mouse model and established protocols for generating preclinical data. Vaccine protection was strongly supported by optimized protocols and we obtained the first evidence of the immune mechanism of protection. We precisely identified the kinetics of vaccine protection and initiated high-throughput single-cell molecular characterization to precisely define the molecular mechanism at play. Anticipating the clinical phase, we prepared a first version of the target product profile and initiated contact with the regulatory agencies. The consortium developed multiple communication platform to reach out to the wide audience and stimulate interactions with key stakeholders. Collectively, these advances (i) provide a biochemical and biophysical characterisation of the vaccine target, which will be leveraged to identify antigens, (ii) define the immunogenicity and protection of the vaccine strategy, which knowledge will be useful for optimizing a vaccine candidate, and (iii) anticipate the next clinical phases, which will derive from the comprehensive pre-clinical datasets generated in the project. After 18-month, the Flavivaccine consortium build upon its multidisciplinary strengths to make strong progresses towards the development of a pan-flavivirus vaccine candidate.
Flavivaccine project started at the beginning of 2024
No achievements or results are ready to be reported
No achievements or results are ready to be reported